The effect of local immunity on gastric cancer prognosis

Aim. To study the state of local immunity in patients with gastric adenocarcinoma. Materials and methods. From 2017 to 2018, 45 previously untreated patients with gastric adenocarcinoma (25 with stage IIII, 20 with stage IV) received surgical/combined treatment or chemotherapy, respectively, at the Blokhin Scientific Research Center of Oncology. Tumor tissue was taken before treatment. By using flow cytometry there were evaluated the percentage of tumor tissue infiltration by lymphocytes (CD45+CD14-TIL); T cells (CD3+CD19-TIL); B cells (CD3-CD19+TIL); NK cell (CD3-CD16+CD56+TIL); effector cells CD16 (CD16+Perforin+TIL) and CD8 (CD8+Perforin+TIL) with their cytotoxic potential active CD16TIL and active CD8TIL; subpopulations of regulatory T cells NKT cells (CD3+CD16+CD56+TIL), regulatory cells CD4 (CD4+CD25+CD127-TIL) and CD8 (CD8+CD11b-CD28-TIL). The prognostic value of immune cells for overall survival (OS) and progression-free survival (PFS) was assessed. Results. A favorable prognosis factor for progression-free survival in patients with local and locally advanced forms of gastric cancer was an increase in the number of CD3-CD19+TIL (HR 0.862, 95% CI 0.7820.957, p=0.005), and an unfavorable prognosis was an increase in NK cells (CD3-CD16+CD56+TIL); HR 1.382, 95% CI 1.0871.758, p=0.008. The negative effect of the relative content of NK cells (CD3-CD16+CD56+TIL) and NKT cells (CD3+CD16+CD56+TIL) on OS of patients with metastatic gastric cancer noted (HR 1.249, 95% CI 0.9971.564, p=0.053; HR 1.127, 95% CI 1.0251.239, p=0.013). At the same time, an increase in the percentage of tumor tissue infiltration by lymphocytes (CD45+CD14-TIL) and an increase in the age of patients (HR 1.005, 95% CI 1.0021.008, p=0.003; HR 1.098, 95% CI 1.0311.170, p=0.004) reduce the incidence of PFS in patients with metastatic gastric carcinoma. Conclusion. Indices of local immunity can serve as additional prognostic factors for gastric carcinoma

Predicting Outcomes in Men With Metastatic Nonseminomatous Germ Cell Tumors (NSGCT): Results From the IGCCCG Update Consortium

Purpose: The classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990. Materials and methods: Data on 9,728 men with metastatic nonseminomatous germ cell tumors treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Europe, North America, and Australia. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS). The survival estimates were updated for the current era. Additionally, a novel prognostic model for PFS was developed in 3,543 patients with complete information on potentially relevant variables. The results were validated in an independent data set. Results: Compared with the original IGCCCG publication, 5-year PFS remained similar in patients with good prognosis with 89% (87%-91%) versus 90% (95% CI, 89 to 91), but the 5-year OS increased from 92% (90%-94%) to 96% (95%-96%). In patients with intermediate prognosis, PFS remained similar with 75% (71%-79%) versus 78% (76%-80%) and the OS increased from 80% (76%-84%) to 89% (88%-91%). In patients with poor prognosis, the PFS increased from 41% (95% CI, 35 to 47) to 54% (95% CI, 52 to 56) and the OS from 48% (95% CI, 42 to 54) to 67% (95% CI, 65 to 69). A more granular prognostic model was developed and independently validated. This model identified a new cutoff of lactate dehydrogenase at a 2.5 upper limit of normal and increasing age and presence of lung metastases as additional adverse prognostic factors. An online calculator is provided (https://www.eortc.org/IGCCCG-Update). Conclusion: The IGCCCG Update model improves individual prognostication in metastatic nonseminomatous germ cell tumors. Increasing age and lung metastases add granularity to the original IGCCCG classification as adverse prognostic factors

The prognostic significance of lactate dehydrogenase levels in seminoma patients with advanced disease: an analysis by the Global Germ Cell Tumor Collaborative Group (G3)

PURPOSE The prognostic significance of lactate dehydrogenase (LDH) in patients with metastatic seminoma is not defined. We investigated the prognostic impact of LDH levels prior to first-line systemic treatment and other clinical characteristics in this subset of patients. METHODS Files from two registry studies and one single-institution database were analyzed retrospectively. Uni- and multivariate analyses were conducted to identify patient characteristics associated with recurrence free survival (RFS), overall survival (OS), and complete response rate (CRR). RESULTS The dataset included 351 metastatic seminoma patients with a median follow-up of 5.36 years. Five-year RFS, OS and CRR were 82%, 89% and 52%, respectively. Explorative analysis revealed a cut-off LDH level of < 2.5 upper limit of normal (ULN) (n = 228) vs. ≥ 2.5 ULN (n = 123) to be associated with a significant difference concerning OS associated with 5-years OS rates of 93% vs. 83% (p = 0.001) which was confirmed in multivariate analysis (HR 2.87; p = 0.004). Furthermore, the cut-off LDH < 2.5 ULN vs. ≥ 2.5 ULN correlated with RFS and CRR associated with a 5-years RFS rate and CRR of 76% vs. 86% (p = 0.012) and 32% vs. 59% (p  ≤  0.001), respectively. CONCLUSIONS LDH levels correlate with treatment response and survival in metastatic seminoma patients and should be considered for their prognostic stratification

Additional file 1: Tables S1-S9. of Assessment of piRNA biogenesis and function in testicular germ cell tumors and their precursor germ cell neoplasia in situ

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